Volz Ann-Kathrin, Frei Alina, Kretschmer Viola, de Jesus Domingues António M, Ketting Rene F, Ueffing Marius, Boldt Karsten, Krämer-Albers Eva-Maria, May-Simera Helen L
Institute of Molecular Physiology, Johannes Gutenberg-University, Mainz, Germany.
Institute of Molecular Biology, Mainz, Germany.
Nat Commun. 2021 Sep 27;12(1):5671. doi: 10.1038/s41467-021-25929-1.
Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis.
初级纤毛是基于微管的感觉细胞器，对于接收和处理细胞信号很重要。最近的研究表明，纤毛还释放细胞外囊泡（EVs）。由于已证明EVs发挥多种生理功能，这些发现有可能改变我们对初级纤毛如何调节特定信号通路的理解。到目前为止，重点一直放在直接从纤毛膜上出芽的大EVs（lgEVs）。纤毛与多泡体衍生的小EVs（smEVs）之间的关联尚未被描述。我们表明，纤毛突变哺乳动物细胞表现出小EVs（smEVs）分泌增加以及EV组成的变化。对smEV货物的表征确定了在纤毛功能障碍时差异装载的信号分子。此外，我们表明这些smEVs具有生物活性，并调节受体细胞中的WNT反应。这些结果为我们提供了对可能是纤毛病发病机制基础的依赖于smEV的纤毛信号传导机制的见解。
